Abstract

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized
by chronic joint inflammation. Knowing which antigens drive the autoreactive T-cell
response in JIA is crucial for the understanding of disease pathogenesis and additionally
may provide targets for antigen-specific immune therapy. In this study, we tested
9 self-peptides derived from joint-related autoantigens for T-cell recognition (T-cell
proliferative responses and cytokine production) in 36 JIA patients and 15 healthy
controls. Positive T-cell proliferative responses (stimulation index ≥2) to one or
more peptides were detected in peripheral blood mononuclear cells (PBMC) of 69% of
JIA patients irrespective of major histocompatibility complex (MHC) genotype. The
peptides derived from aggrecan, fibrillin, and matrix metalloproteinase (MMP)-3 yielded
the highest frequency of T-cell proliferative responses in JIA patients. In both the
oligoarticular and polyarticular subtypes of JIA, the aggrecan peptide induced T-cell
proliferative responses that were inversely related with disease duration. The fibrillin
peptide, to our knowledge, is the first identified autoantigen that is primarily recognized
in polyarticular JIA patients. Finally, the epitope derived from MMP-3 elicited immune
responses in both subtypes of JIA and in healthy controls. Cytokine production in
short-term peptide-specific T-cell lines revealed production of interferon-γ (aggrecan/MMP-3)
and interleukin (IL)-17 (aggrecan) and inhibition of IL-10 production (aggrecan).
Here, we have identified a triplet of self-epitopes, each with distinct patterns of
T-cell recognition in JIA patients. Additional experiments need to be performed to
explore their qualities and role in disease pathogenesis in further detail.